Suicide is a worldwide public health problem with more than 800,000 deaths due to suicide each year. Rates of suicide are far exceeded by suicide attempts, which occur up to 20 times more frequently, making suicidality a huge personal, social and economic burden. These stark figures highlight the urgent need for improved prevention and treatment, however, progress has been hampered by the lack of reliable methods for predicting suicidality and a poor understanding of its biological etiology.
Like many psychiatric disorders, suicide attempt is known to have a partially genetic underpinning and genetic studies can provide invaluable insights into the underlying biology. Through the collective efforts of many researchers, we analyzed the genomes of suicide attempters and non-attempters across three major psychiatric disorders. Our data showed that suicide attempters with major depressive disorder, bipolar disorder or a schizophrenia diagnosis carry a greater genetic liability for major depression than non-attempters. These results indicate the existence of a shared genetic etiology between suicide attempt and major depression that is common to suicide attempt in different psychiatric disorders. However, further collaborative efforts to amass samples on an even larger scale will be essential to identify specific genetic variants which play a role in increasing risk of suicide attempt. The ultimate goal of this research is to undercover the biological mechanisms underlying suicidality and develop new treatments and preventions, in order to reduce its burden on patients, families and healthcare systems.
Investigations of the genetic overlap between internalising psychiatric disorders and co-morbid physical health disorders.
Identify changes in DNA that increase the risk for psychiatric disorders alone (specifically the internalising disorders: depression, anxiety including OCD, and related disorders), and for these disorders in the presence of co-morbid physical disorders (autoimmune disorders, including rheumatoid arthritis, and non-immune disorders, including type 2 diabetes, migraine, chronic pain, obesity and body-mass index). Disorder status will be determined from the UK Biobank adjudicated health outcomes, including data from primary care , hospitals, and self-report. We will also explore whether the variants associated with each psychiatric disorder predict the likelihood that an individual has a given physical disorder. Understanding how genetics influence psychiatric disorders, and the relationship between psychiatric and physical disorders, will provide much-needed insight into the underlying biology. As well as increasing our understanding of interactions between the brain and body, this may identify target systems for the development of novel treatments in psychiatry; for example, the re-purposing of anti-inflammatory drugs for the treatment of schizophrenia and depression is a promising area of ongoing research. Furthermore, identification of shared genetic risk factors could assist in diagnosis by determining whether a given patient is high or low risk. Genotype information is being produced on the UK Biobank sample. We will use this to perform genome-wide association studies using publicly-available software packages, testing thousands of DNA variants for their association with different disorders. We will compare individuals with internalising disorders to controls, as well as comparing those with both a psychiatric and a physical disorder to those with only one (to identify genetic variants associated with having both disorders).
We will also explore the genetic overlap between a given psychiatric disorder and associated physical disorders, using the results from the association studies and publicly-available software packages. Full cohort
|Lead investigator:||Dr Gerome Breen|
|Lead institution:||King's College London|
4 related Returns
|Return ID||App ID||Description||Archive Date|
|4006||16577||Genetic comorbidity between major depression and cardio-metabolic traits, stratified by age at onset of major depression||14 Oct 2021|
|2690||16577||Genome-wide gene-environment analyses of major depressive disorder and reported lifetime traumatic experiences in UK Biobank||30 Oct 2020|
|2708||16577||Indicators of mental disorders in UK Biobank - A comparison of approaches||30 Oct 2020|
|2663||16577||Mental health in UK Biobank - development, implementation and results from an online questionnaire completed by 157,366 participants: a reanalysis||29 Oct 2020|
|2644||GWAS of Suicide Attempt in Psychiatric Disorders and Association With Major Depression Polygenic Risk Scores||Mullins et al||2019||The American Journal of Psychiatry (2019)|